Gaucher's disease is an inherited disorder caused by a mutation of the gene for the enzyme glucocerebrosidase. The normal gene has now been cloned by several laboratories and at least two have inserted the cDNA into retroviral vectors and obtained expression of the enzyme in cell lines from patients following gene transfer. However, retroviral vectors produced to a high titer and stability containing this gene have not been made yet. It is the aim of this project to design vectors that can generate high titer helper-free recombinant viruses that contain appropriate promoters and/or enhancers leading to expression of the glucocerebrosidase gene following gene transfer into bone marrow stem cells and embryonic stem cells. Gene therapy" of mice with the human glucocerebrosidase gene and creation of transgenic mice using these vectors will help evaluate the feasibility and efficiency of retroviral gene therapy for Gaucher disease.